Regulation of blood-brain barrier integrity by brain microvascular endothelial cells in ischemic stroke: A therapeutic opportunity

被引:0
|
作者
Tang, Ziqi [1 ]
Li, Ruoxi [2 ]
Guo, Xi [3 ,4 ,5 ]
Wang, Zhongyu [6 ,7 ]
Wu, Jianping [1 ,3 ,4 ,5 ,7 ]
机构
[1] Wuhan Univ Technol, Sch Chem Chem Engn & Life Sci, Wuhan 430070, Peoples R China
[2] Columbia Univ, Irving Med Ctr, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA
[3] Capital Med Univ, Beijing Tiantan Hosp, Beijing 10070, Peoples R China
[4] China Natl Clin Res Ctr Neurol Dis, Beijing 10070, Peoples R China
[5] Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing 10070, Peoples R China
[6] Guangxi Med Univ, Sch Basic Med Sci, Nanning 530021, Peoples R China
[7] Hubei Univ Med, Sch Basic Med Sci, Dept Pharmacol, Shiyan 440070, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
Blood-brain barrier; Ischemic stroke; Brain microvascular endothelial cells; Transporters; Ion channels; Astrocytes; ORGANIC CATION TRANSPORTERS; INDUCED DOPAMINERGIC TOXICITY; CEREBRAL-ARTERY OCCLUSION; ZONULA OCCLUDENS-1 AND-2; P-GLYCOPROTEIN; EXTRACELLULAR-MATRIX; RESISTANCE PROTEIN; TIGHT-JUNCTION; NA+/CA2+ EXCHANGER; ADHESION MOLECULE;
D O I
10.1016/j.ejphar.2025.177553
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Stroke is the second leading cause of death from cardiovascular diseases. Brain microvascular endothelial cells (BMECs) are crucial in the treatment of cerebral ischemic stroke, as their functional status directly affects the integrity of the blood-brain barrier (BBB). This review systematically discusses the central role of BMECs in ischemia. The mitochondrial dysfunction and activation of apoptosis/necrosis pathways in BMECs directly disrupt the integrity of the BBB and the degradation of junctional complexes (such as TJs and AJs) further exacerbates its permeability. In the neurovascular unit (NVU), astrocytes, microglia, and pericytes regulate the function of BMECs by secreting cytokines (such as TGF-beta and VEGF), showing dual effects of promoting repair and damage. The dynamic changes of transporters, including those from the ATP-binding cassette and solute carrier families, as well as ion channels and exchangers, such as potassium and calcium channels, offer novel insights for the development of targeted drug delivery systems.
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页数:19
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